Prognostic Impact of COVID-19 Inflammation Score Response: A Sub-Group Analysis on Critically Ill Patients of the RuxCoFlam Trial

TL;DR

This study shows that a reduction in the COVID-19 inflammation score (CIS) after treatment with ruxolitinib is linked to better survival in critically ill patients.

Contribution

The study identifies CIS response and patient age as novel predictors of survival in critically ill COVID-19 patients treated with ruxolitinib.

Findings

62 out of 81 patients showed a 25% or greater reduction in CIS after 7 days of treatment.

CIS responders had a significantly higher 60-day survival rate (74%) compared to non-responders (32%).

Younger age and CIS response were independently associated with improved survival probability.

Abstract

This study aims to identify parameters predicting COVID-19 inflammation score (CIS) response and survival probability in critically ill patients with hyperinflammation treated with the Janus kinase (JAK) 1/2 inhibitor ruxolitinib. This is a single arm, non-randomized, open-label, phase-II study for frontline treatment in adults in the intensive care unit (ICU). Ninety-two critically ill COVID-19 patients with CIS ≥ 10 were treated in the RuxCoFlam trial (NCT04338958) with ruxolitinib between April 2020 and June 2021. Median ICU treatment duration was 15 days (range, 2–73). Out of 81 evaluable patients, 62 (77%) showed CIS reduction ≥ 25% on day 7 (CIS response). In multiple logistic regression analyses, higher CIS on day 0 (odds ratio (OR), 1.56; 95% confidence interval (CI), 1.01–2.41; p = 0.046) and male gender (OR, 4.76; 95% CI, 1.22–16.67; p = 0.024) were significantly associated with CIS response. Sixty-day survival probability was higher in CIS-responders compared to non-responders (74% vs. 32%; p < 0.001). Multiple Cox regression analysis revealed younger age (10-year difference) (hazard ratio (HR), 0.65; 95% CI, 0.46–0.91; p = 0.012) and CIS response (HR, 0.19; 95% CI, 0.08–0.45; p < 0.001) as significant parameters for survival probability. In conclusion, reduced risk of death in CIS-responders underlines the usefulness of CIS for the assessment of hyperinflammatory disorders, such as COVID-19, under JAK1/2 inhibitor therapy.

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